Doxorubicin-induced acute cardiotoxicity is associated with increased oxidative stress, autophagy, and inflammation in a murine model.

Autor: Dulf PL; Iuliu Hatieganu University of Medicine and Pharmacy, 400012, Cluj-Napoca-Napoca, Romania., Mocan M; Emergency Clinical County Hospital, 40006, Cluj-Napoca-Napoca, Romania. mihaela.mocan@gmail.com.; Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012, Cluj-Napoca-Napoca, Romania. mihaela.mocan@gmail.com., Coadă CA; Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138, Bologna, Italy. camelia.coada@unibo.it.; Department of Molecular Sciences, Iuliu Hatieganu University of Medicine and Pharmacy, 400394, Cluj-Napoca-Napoca, Romania. camelia.coada@unibo.it., Dulf DV; Iuliu Hatieganu University of Medicine and Pharmacy, 400012, Cluj-Napoca-Napoca, Romania.; Medisprof Cancer Center, 400641, Cluj-Napoca-Napoca, Romania., Moldovan R; Department of Functional Biosciences, Iuliu Hatieganu University of Medicine and Pharmacy, 400012, Cluj-Napoca-Napoca, Romania., Baldea I; Department of Functional Biosciences, Iuliu Hatieganu University of Medicine and Pharmacy, 400012, Cluj-Napoca-Napoca, Romania., Farcas AD; Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012, Cluj-Napoca-Napoca, Romania., Blendea D; Department of Internal Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 400012, Cluj-Napoca-Napoca, Romania.; Department of Cardiology, Heart Institute, 40001, Cluj-Napoca-Napoca, Romania., Filip AG; Department of Functional Biosciences, Iuliu Hatieganu University of Medicine and Pharmacy, 400012, Cluj-Napoca-Napoca, Romania.
Jazyk: angličtina
Zdroj: Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 2023 Jun; Vol. 396 (6), pp. 1105-1115. Date of Electronic Publication: 2023 Jan 16.
DOI: 10.1007/s00210-023-02382-z
Abstrakt: Drug-induced cardiotoxicity is a life-threatening side effect of doxorubicin (DOX) treatment that impacts patient prognosis and survival. In the majority of cases, the acute clinical form often remains asymptomatic, with few patients presenting rather nonspecific electrocardiographic abnormalities. While chronic toxicity has been more widely studied, the alterations appearing in acute cardiotoxicity are much less investigated. Thus, our in vivo study aimed to evaluate the process of DOX-induced acute myocardial toxicity by investigating oxidative stress and autophagy markers as mechanisms of myocardial toxicity in correlation with echocardiography and electrocardiography findings. Our results show that both autophagy and oxidative homeostasis were disrupted as soon as 7 days after DOX treatment, alterations that occurred even before the significant increase of NT-proBNP, a clinical marker for cardiac suffering. Moreover, we found a large number of alterations in the electrocardiography and echocardiography of treated rats. These findings suggest that DOX-induced myocardial toxicity started early after treatment initiation, possibly marking the initial phase of the unfolding process of cardiac damage. Further studies are required to completely decipher the mechanisms of DOX-induced cardiotoxicity.
(© 2023. The Author(s).)
Databáze: MEDLINE
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